JP4494770B2 - Crystallization method and crystallizer - Google Patents

Description

  The present invention relates to an organic acid crystallization method including adding an acid to an organic acid salt solution to crystallize the organic acid, and a crystallization apparatus suitable for the method.

  In general, crystallization of an organic acid that is hardly or insoluble in water, such as carboxylic acid, is called so-called neutralized crystallization in which the salt is crystallized by reacting with an acid in the presence of water. It is carried out by reaction crystallization.

  As such neutralized crystallization, for example, there is known a method of producing an organic acid crystal by adding an acid to an aqueous solution of a water-soluble salt of a crystalline organic acid such as adipic acid or nicotinic acid. (For example, refer nonpatent literature 1.).

  In the neutralization crystallization method, an acid is dropped on the surface of the alkaline aqueous solution of the organic compound charged in the container using a pump or the like, or in the alkaline aqueous solution of the organic compound charged in the container, Crystals of the organic compound are deposited by dropping acid using a dip tube.

According to the description of Non-Patent Document 1, when hydrochloric acid is dropped into a sodium nicotinate aqueous solution, first, the (I) unsaturated state of nicotinic acid exceeds (II) the saturated solubility of nicotinic acid. After passing through the supersaturated state in which no crystals are precipitated, (III) the supersaturated state is rapidly eliminated by crystal precipitation, and (IV) crystal precipitation in the saturated state is performed.
Fang Wang and 1 other, “Monitoring pH Swing Crystallization of Notice Acid by the Use of Attenuated Total Reflection Fourier Transform Infrared Spectrometry”, “Ind. Eng. Chem. Res. Vol.39, No.6, 2000”, p.2101 -2104

However, when the inventors of the present invention reacted the monosodium adipic acid salt with hydrochloric acid by the method described in Non-Patent Document 1, the average particle size of the obtained crystals was as small as 129 μm, and the bulk density of the crystals However, only crystals of adipic acid as small as 267 kg / m ³ could be obtained.

  Thus, the conventional neutralized crystallization method can only obtain crystals with a small average particle diameter and bulk density. For this reason, for example, when the crystals obtained by crystallization are filtered out, It has problems such as taking time.

  The present invention has been made in view of the above-mentioned problems, and the object thereof is a crystal capable of producing a crystal having a larger average particle diameter than a conventional crystallization method called so-called neutralization crystallization. It is to provide an analysis method.

  As a result of diligent studies to achieve the above object, the inventors of the present application have (IV) saturation as one of the factors that can obtain only a crystal having a small average particle diameter even using the above-described conventional neutralization crystallization method. It was concluded that many new nucleations occurred during the state and especially during the period of rapid supersaturation due to (III) crystal precipitation. In other words, the inventors of the present application, as a result of the study, can obtain only crystals having a small average particle diameter because many of the raw material compounds used for the crystallization reaction precipitate as nuclei and are hardly used for crystal growth. It came to the idea that it was not possible.

  Therefore, the inventors of the present application conducted further studies to increase the proportion of the compound used for crystal growth, and as a result, a portion of the fine crystal derived from the nucleus generated by the dropwise addition of the acid was converted to a salt with a base. It was found that the salt can be used for crystal growth by dissolving and reacting the salt with an acid again.

  In the crystallization method according to the present invention, in the presence of crystals, the pH hardly fluctuates even when an acid or a base is added. This is because, in the crystallization method according to the present invention, even if a base is added, the organic acid only becomes a salt, and the pH does not change greatly by the addition of the base. For this reason, in the neutralization crystallization in which the crystallization reaction is carried out by adding an acid to bring the reaction solution to a neutral pH or lower, for example, once the crystals are produced, the pH varies substantially even if a base is added. By not doing so, it seems impossible to control the crystallization reaction. However, the inventors of the present application have found that the above-mentioned reaction occurs by adding a base during the crystallization, and further controlling the above-mentioned crystallization reaction by controlling the ratio of the acid to be added. I found out that it can be controlled. In the present invention, the amount of acid required for crystallization varies depending on the amount of base used.

  That is, in order to solve the above-described problem, the organic acid crystallization method according to the present invention converts a part of the organic acid crystal into an organic acid salt and dissolves it by adding a base to the organic acid crystal-containing liquid. And adding an acid to the organic acid salt solution.

  According to the above configuration, fine crystals can be reduced, and the proportion of the compound used for crystal growth can be increased and crystal growth can be efficiently performed. However, there is an effect that a large crystal can be obtained stably with good reproducibility.

  In addition, in order to solve the above-described problem, the method for crystallizing an organic acid according to the present invention adds an acid to a solution of an organic acid salt so that at least a part of the total organic acid crystals to be precipitated is obtained. Precipitating and adding a base to the organic acid crystal-containing liquid converts a part of the organic acid crystal thus precipitated into an organic acid salt to dissolve it, and then adds an acid to the organic acid salt solution. May be included.

  According to the above configuration, fine crystals can be reduced, and the proportion of the compound used for crystal growth can be increased and crystal growth can be efficiently performed. However, there is an effect that a large crystal can be obtained stably with good reproducibility.

  The organic acid crystallization method according to the present invention is an organic acid crystallization method comprising adding an acid to a solution of an organic acid salt to crystallize the organic acid in order to solve the above problems. Then, after the organic acid starts to crystallize by the addition of the acid, a base is added to the liquid containing the organic acid crystal to convert a part of the crystal of the organic acid into an organic acid salt and dissolve the acid. May be added. In this crystallization method, addition of an acid and addition of a base are performed in separate reaction vessels provided in communication with each other while circulating the solution in the reaction vessel between the reaction vessels, and the initial acid is added. The amount of organic acid salt (g) in the organic acid salt solution before addition is P, the value obtained by dividing the molecular weight of the organic acid salt by the number of anionic functional groups of one molecule of the organic acid salt is Z, and the amount of base added The value obtained by dividing (g) by the equivalent (g) of the base is M, the addition time is T (min), the circulation amount of the liquid per unit time is F (ml / min), and the maximum liquid amount in the system is When the logarithmic average of the minimum liquid volume is L (ml), the value of the formula represented by L × M / (T × F × P × Z) is 0.5 or more and less than 1.5 so as to satisfy It is preferable to adjust the amount of the base.

  According to the above configuration, when the supersaturation degree of the target organic acid is very small and crystals are precipitated immediately in the vicinity of the acid dropping, nucleation is dominant and crystal growth is poor. However, by dissolving fine crystals derived from new nucleation with a base, the fine crystals are reduced and the amount of organic acid salt used for crystal growth is increased, so that the crystal grain size can be stabilized with good reproducibility. Can be bigger.

Moreover, in the organic acid crystallization method according to the present invention, it is preferable that the following M / (P × Z) is in a range satisfying the following formula.
Q / (P × Z) −0.3 ≦ M / (P × Z) ≦ Q / (P × Z) −0.03
M: Value obtained by dividing the amount of base added (g) by the equivalent amount (g) of the base Q: Value P obtained by dividing the amount of acid added (g) added before the base addition by the equivalent amount (g) of the acid : Amount of organic acid salt in organic acid salt solution before initial acid addition (g)
Z: Value obtained by dividing the molecular weight of the organic acid salt in the organic acid salt solution before the addition of the initial acid by the number of anionic functional groups of one organic acid salt molecule According to the above configuration, the crystal growth period becomes long, High effect can be obtained.

  Further, the amount of organic acid crystals remaining after the addition of the base is preferably in the range of 1 to 30% by weight of the total crystals to be precipitated. According to said structure, a crystal growth period becomes long and can acquire a high effect.

  Moreover, in order to solve the said subject, the manufacturing method of the organic acid crystal concerning this invention has the process of obtaining an organic acid crystal using the organic acid crystallization method concerning this invention, and the organic acid obtained by this process And a step of isolating the organic acid crystal from the reaction solution containing the crystal.

  According to the above configuration, fine crystals can be reduced, and the proportion of the compound used for crystal growth can be increased and crystal growth can be efficiently performed. However, there is an effect that a large organic acid crystal can be stably obtained with good reproducibility.

  In order to solve the above problems, the crystallization apparatus according to the present invention includes a crystallization reaction vessel, an acid supply means for supplying an acid into the crystallization reaction vessel, and a base in the crystallization reaction vessel. A base supply means for supplying, wherein the acid supply means and the base supply means include supplying the acid and the base to positions separated from each other in the crystallization reaction vessel.

  According to said structure, there exists an effect that the crystal | crystallization with a large average particle diameter and a large bulk density can be obtained stably with sufficient reproducibility.

  The crystallization apparatus according to the present invention includes a first reaction vessel provided with an acid supply unit, a second reaction vessel provided with a base supply unit, the first reaction vessel and the second reaction vessel, And a liquid circulating means for circulating the reaction liquid between the first reaction container and the second reaction container.

  According to said structure, there exists an effect that the crystal | crystallization with a large average particle diameter and a large bulk density can be obtained stably with sufficient reproducibility.

  According to the present invention, a part of crystals crystallized by reacting a raw organic acid salt with an acid is converted into an organic acid salt by a base and dissolved, and this organic acid salt-containing liquid is dissolved in the presence of the remaining crystals. By reacting with the acid again, fine crystals can be reduced, and the proportion of the compound used for crystal growth can be increased and the crystals can be efficiently grown, so the average particle size is large. In addition, there is an effect that crystals having a large bulk density can be stably obtained with good reproducibility.

  The crystallizer according to the present invention is suitably used for the above crystallization reaction, and by using the crystallizer, a crystal having a large average particle diameter and a large bulk density can be stably obtained with good reproducibility. There is an effect that can be.

An embodiment of the present invention will be described in detail below.
The crystallization method according to the present embodiment is a crystallization method in which an acid is added to an organic acid salt solution to precipitate a crystal, and the organic acid crystal crystallized by reacting the organic acid salt with an acid. In this method, a part is dissolved with a base, and the dissolved organic acid salt is reacted again with an acid in the presence of the remaining organic acid crystals.

  More specifically, in the crystallization method according to the present embodiment, the organic acid salt is converted into a raw material compound for crystallization, that is, a starting material at the start of the crystallization reaction (hereinafter referred to as a raw material organic acid salt). And a solution of the starting organic acid salt, preferably by adding an acid to the aqueous solution and reacting the organic acid salt with the acid to produce the desired organic acid crystal. After the raw material organic acid salt to be provided is reacted with an acid to crystallize at least a part of the target organic acid, a part of the organic acid crystal precipitated by the crystallization is converted into an organic acid salt with a base. In this state, an acid is added to the organic acid salt solution and the organic acid salt in the system is reacted with the acid again in the state where the remaining crystals are present.

  The crystallization method according to this embodiment can be broadly divided into the following two methods.

  The first method involves reacting a raw material organic acid salt with an acid to crystallize the target organic acid. The positive reaction from the raw material to the target product and once precipitated organic acid crystals are dissolved again with a base. In this method, the reverse reaction from the target product to the raw material is performed independently, and (1) the above normal reaction and reverse reaction are alternately performed to reverse the above normal reaction. This is a method of performing the reaction with a time difference. Examples of the method include a method of performing the above-described normal reaction and reverse reaction at different times in the same region by alternately performing the above-described normal reaction and reverse reaction in the same container. In the above method, after the normal reaction, the reaction solution in the reaction is transferred to another container and the reverse reaction is performed.For example, the reaction solution after each reaction is transferred to another container and the reaction in the next step is performed. By performing, you may perform a normal reaction and a reverse reaction alternately.

  As a preferred example of the first method, at least a part of the organic acid to be precipitated is crystallized by adding an acid to the solution of the starting organic acid salt, and the base is added to the organic acid crystal-containing liquid to add the organic acid. A method for crystallizing an organic acid, which comprises converting a part of an acid crystal into an organic acid salt and dissolving it, and adding an acid to the organic acid salt solution. In the crystallization method of depositing an acid to precipitate an organic acid crystal, after depositing at least a part of the total organic acid crystal deposited when the organic acid salt is completely reacted with the acid, A base is added to the organic acid crystal-containing solution to convert a part of the organic acid crystals into an organic acid salt and dissolve, and then an acid is further added to the organic acid salt solution to dissolve the dissolved organic acid. There is a method in which the salt is reacted with an acid again in the presence of the remaining organic acid crystals. More specifically, an organic acid salt is used as a raw material compound, and an acid is added to a solution of the organic acid salt, preferably an aqueous solution, to react the raw material organic acid salt with an acid, whereby at least one of the corresponding organic acids is reacted. After crystallizing a part, a base is added to the organic acid crystal precipitated by the crystallization, and a part of the crystal is reacted with the base to convert it into an organic acid salt to be dissolved. In this method, an acid is added to the salt solution and the organic acid salt is reacted again with the acid in the presence of the remaining crystals, and the remaining crystals are grown as nuclei (seed crystals).

  That is, in the first method, the crystallization according to the present embodiment, that is, the raw organic acid salt used for neutralization crystallization is dropped in the presence of water, and the target organic acid is (I) From an unsaturated state, (II) after passing through a supersaturated state where crystals do not precipitate exceeding the saturation solubility of the organic acid, (III) after the rapid supersaturated state is eliminated by crystal precipitation, (IV) saturated state (V) The base is added at any point of time, and the amount of the acid excluding the neutralization by the base is returned to the point of (II), so that it is considered that the fine particles are precipitated at the time of the above (III) and (IV). This is a method in which crystals (relatively small crystals among the precipitated crystals) are dissolved, and (VI) the acid is added again to transfer the dissolved portion to crystal growth.

  On the other hand, the second method is a method in which the above-described normal reaction and reverse reaction are simultaneously performed in parallel. For example, (2) Alternatively, (3) the addition of the acid and the addition of the base are performed in separate containers provided in communication with each other while the liquid in the container is circulated between the containers. This is a method of performing the normal reaction and the reverse reaction. In the above method (2), by supplying the acid and base to a position separated from each other by dropping or the like, the region in which the normal reaction (crystal precipitation area) is performed in the same container and the region in which the reverse reaction is performed (partial) And a normal reaction and a reverse reaction are performed in a non-uniform state.

  Specifically, the second method is a method for crystallizing an organic acid, which comprises crystallization of an organic acid by adding an acid to a solution of a raw material organic acid salt. After the beginning, the acid is added by adding a base to the reaction system while dissolving a part of the organic acid crystal. More specifically, by supplying a base to an organic acid crystal-containing liquid crystallized by reacting an organic acid salt with an acid, and reacting the organic acid salt with the acid while dissolving a part of the crystal again. is there.

  In other words, the second method is a method of simultaneously adding a base to an organic acid salt while supplying an acid, and mainly dissolves fine crystals derived from new nucleation in a saturated state of (IV) with a base. In this method, an excess acid is added to dissolve the dissolved component for crystal growth.

  Of the two methods described above, the first method is a rapid saturation process due to (III) crystal precipitation through a supersaturated state in which crystals do not precipitate even if the saturation solubility of the target organic acid is exceeded, as shown in (II) above. When the supersaturated state is eliminated, the supersaturation degree is very large, and it is suitable for the case where crystals are precipitated all at once during the dropping.

  Thus, during the acid dropping, for example, when the crystal does not come out with supersaturation until the beginning of the dropping or just before the dropping, and the crystal is precipitated all at once during the dropping, the nucleation is dominant and the crystal growth is difficult. The diameter tends to be small.

For this reason, if a base is added at an arbitrary time after crystal precipitation, that is, after the rapid supersaturation state of (III) is eliminated, at any time in the state of (IV), the crystal precipitated in (IV) , It is dissolved from the small particle size. This is because the crystal having a smaller particle size has a larger specific surface area, so that when the crystal precipitated in (IV) is dissolved and the acid is dropped again in (V), the crystal has already been removed. Since crystals exist in the system, crystal growth is likely to occur with the crystals remaining without being dissolved as nuclei (seed crystals).

  More specifically, by way of example, when the supersaturation degree of the organic acid is very large and the supersaturation state continues for a long time, for example, P is the amount of raw material organic acid salt (g), and the molecular weight of the raw material organic acid salt is When the value obtained by dividing the organic acid salt molecule by the number of anionic functional groups is Z and the value obtained by dividing the acid addition amount (g) by the equivalent amount (g) of the acid is Q ′, Q ′ / (P When an organic acid crystal is deposited for the first time when an amount such that × Z) is 0.8 is dropped, primary nuclei on which the crystal has not grown are deposited all at once.

  For this reason, in such a case, the precipitated crystals grow only for the remaining 20%. Therefore, when, for example, 80% of the precipitated crystals are dissolved, the amount of the remaining organic acid salt in the reaction solution increases, while the remaining 20% of the crystals remain. The ratio of the acid salt is remarkably increased as compared with that before the crystal is dissolved, and the amount of the organic acid salt used for crystal growth is remarkably increased. Therefore, when an acid amount corresponding to the remaining organic acid salt is dropped again, the remaining crystal grows using the crystal as a nucleus (seed crystal), and a large crystal can be stably obtained with good reproducibility. Become.

  That is, in the first method, when the supersaturation degree of the target organic acid is very large and crystals are precipitated all at once during acid dropping, nucleation is dominant and crystal growth is poor. By dissolving the portion, the fine crystal is reduced and the amount of organic acid salt used for crystal growth is increased to stably increase the crystal grain size with good reproducibility.

  Therefore, the first method can be suitably used for crystallization of an organic acid having a relatively high degree of supersaturation such as nicotinic acid and salicylic acid.

  In the first method, Q ′ / (P × Z) in the range of (II) is usually in the range of 0.1 to 1.0, preferably in the range of 0.3 to 1.0. It is preferably used for a certain compound.

  On the other hand, when the degree of supersaturation is very small and crystals immediately precipitate in the vicinity of acid dropping, new nucleation occurs one after another by dropping the acid, that is, generation of fine crystals. It is preferable to use the second method.

  That is, in the second method, when the supersaturation degree of the target organic acid is very small and crystals are precipitated immediately in the vicinity of acid dropping, nucleation is dominant and crystal growth is poor. While precipitating, the fine crystals derived from the generation of new nuclei are dissolved with a base, thereby reducing the fine crystals and increasing the amount of organic acid salt used for crystal growth to stabilize the crystal grain size with good reproducibility. Can be increased.

  Even when the second method is adopted, since the crystal having a smaller particle size has a larger specific surface area, the acid is always excessive with respect to the base, that is, the amount exceeding the neutralization by the base. By dropping the acid, only newly generated fine crystals are completely dissolved, and the remaining crystals that are not completely dissolved react with the acid to further grow. Therefore, by repeating this, even when the supersaturation degree of the target organic acid is very small and crystals immediately precipitate in the vicinity of acid dropping, the amount of raw material compounds used for crystal growth is reduced while reducing fine crystals. It is possible to increase the grain size of the crystals present as nuclei.

  Usually, when the range of (II) occupying the dropping time is large, a large amount of fine crystals are precipitated in (III), so that the first method has the effect of increasing the particle size than the second method. large. On the contrary, if the range of (II) occupying the dropping time is small, as in the case where crystals are precipitated immediately after the acid is dropped, the range of (IV) occupying the dropping time becomes large, so The effect of increasing the particle size is greater in the second method than in the first method. However, except for the case where there is no range of (IV), the second method always works effectively.

  Therefore, the second method is not limited to neutral crystallization in general, that is, not only a compound having a relatively high degree of supersaturation such as adipic acid but also a compound having a little supersaturation such as biotin. It can be used suitably.

  The second method is suitably used for organic acids in which Q ′ / (P × Z) is usually 0.4 or less, preferably 0.1 or less within the range of (II).

  The organic acid applicable in the present invention is a compound having a carboxyl group, a sulfonic acid group, a sulfenic acid group, a phosphonic acid group, a phenolic hydroxyl group and the like having a melting point of 50 ° C. or higher, adipic acid, palmitic acid, stearic acid, Aliphatic carboxylic acids such as biotin, aromatic carboxylic acids such as benzoic acid, nicotinic acid and salicylic acid, aromatic sulfonic acids such as benzenesulfonic acid, aromatic sulfenic acids such as phenylsulfenic acid, and aromatics such as phenylphosphonic acid Examples thereof include phenol derivatives such as phosphonic acid, bisphenol A, xylenol, and naphthol. The organic acid salt is a salt that is soluble in the organic acid solvent described above, and examples thereof include alkali metal salts such as sodium salt and potassium salt.

  The raw material organic acid salt is subjected to the crystallization reaction as a solution of the raw material organic acid salt. In the solution, the organic acid salt becomes an anion, reacts with the acid to precipitate an organic acid crystal, and reacts with the base to dissolve the crystal.

  The organic acid salt may be one obtained by dissolving an organic acid in a base when the above-described crystallization is intended for purification.

  The organic acid salt reacts with the acid or base in the presence of water to react with the acid or base to crystallize or dissolve.

  In this embodiment, for example, an organic acid salt solution prepared by dissolving an organic acid salt in water or alkali, preferably an organic acid salt aqueous solution as a reaction stock solution, and an acid and / or a base in the reaction stock solution. However, the present invention is not limited to this. For example, when an acid or a base is added later to an organic acid salt, the acid or base is added. Water may be added together with the base. Further, even when the raw material organic acid salt solution is prepared in advance, an acid and / or a base may be mixed with water and added.

  Examples of the solvent for dissolving the organic acid salt include an aqueous solvent, specifically, for example, water; an organic solvent mixed with water; or a mixture thereof. The solvent is not particularly limited as long as it is uniformly mixed with water, but water is most preferable.

  Specific examples of the organic solvent include methanol, ethanol, isopropanol, acetone, tetrahydrofuran, dioxane, N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide, and the like. It is not limited. Only one kind of these organic solvents may be used, or two or more kinds may be appropriately mixed and used.

  The base used may be any base that can dissolve the organic acid by adding the base, such as sodium hydroxide, potassium hydroxide, ammonia gas, aqueous ammonia, potassium carbonate, sodium carbonate, sodium bicarbonate. Preferably, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium bicarbonate can be mentioned. In the present invention, the cation part of the raw material organic acid salt and the cation part of the base used are preferably the same.

  In addition, the acid to be used may be any combination with the solvent to be used, as long as the solubility of the target compound is small, that is, the one that can react with the raw material compound and crystallize the target compound. Examples thereof include ammonium sulfate, carbon dioxide gas, hydrochloric acid gas, SOx, NOx and the like. Among these acids, hydrochloric acid and sulfuric acid are preferable because they are easy to handle.

  The crystallization method according to the present embodiment is suitably used, for example, for the production of crystals at a neutral or lower pH.

  The crystallization method according to the present embodiment is particularly effective for crystallization of an organic acid that is hardly soluble or insoluble in water as described above, and can be suitably used for the production of such an organic acid crystal.

  In the crystallization method according to the present embodiment, an organic acid crystal once precipitated by crystallization is finally converted to an organic acid salt with a base at what time and to what extent the acid required finally. The amount added is determined.

The first method and the second method will be specifically described below with reference to the drawings.
First, the first method will be described.

  Examples of the reaction vessel (crystallization reaction tank) used in the first method include a stirring tank equipped with a stirrer equipped with a disk turbine blade, a paddle blade, a retracted blade such as a three-sheet retracted blade, an anchor blade, and the like. However, the reaction vessel is not particularly limited as long as it can be used for the reaction of an organic acid salt as a raw material with an acid and a base, and its scale (capacity), shape, material, etc. There is no particular limitation.

  As the reaction vessel, a reaction vessel having a jacket capable of cooling or heating the reaction liquid in the reaction vessel through the reaction vessel by conduction of a refrigerant or a heat medium, for example, is preferably used on the outer wall side of the reaction vessel. It is done. The reaction vessel having such a jacket facilitates control of the reaction temperature, such as removal of heat of neutralization.

The stirring rotation speed by the stirrer (stirring blade) is preferably set so that the stirring power per unit volume in the reaction vessel is in the range of 0.05 to 2.0 kW / m ^3. More preferably, it is set to be within the range of 0.4 kW / m ³ .

  Furthermore, the reaction vessel may have a baffle such as a plate baffle, a beaver tail baffle, a finger baffle, a disk baffle, a donut baffle, etc. in addition to the stirring blade.

FIG. 1 shows an example of a crystallization apparatus suitably used for the first method.
A crystallization apparatus 1 shown in FIG. 1 includes a reaction vessel 2 as a crystallization reaction tank used for a crystallization reaction, an acid supply line 3 (acid supply means) for supplying an acid into the reaction vessel 2, and the reaction. A base supply line 4 (base supply means) for supplying a base into the container 2 is provided.

  The reaction vessel 2 is provided with a stirrer 5 for stirring and reacting the reaction stock solution introduced into the reaction vessel 2. In addition, the reaction vessel 2 includes a jacket 6 having a conduction port (not shown) serving as an inlet or outlet of a heat medium such as hot water on the outer wall side.

  The acid supply line 3 includes an acid storage tank 7 for storing acid, hollow connection pipes 8 and 9 serving as an acid supply path (flow path), and a dropping pipe 10 for dropping and supplying acid into the reaction vessel 2. In addition, an acid supply pump 11 is provided so as to be interposed between the connecting pipes 8 and 9 and sends the acid stored in the acid storage tank 7 to the dropping pipe 10 through the connecting pipes 8 and 9. It has.

  The base supply line 4 includes a base storage tank 12 for storing a base, hollow connection pipes 13 and 14 serving as a base supply path (flow path), and a drop for supplying the base into the reaction vessel 2 dropwise. A base 15 is provided for intervening the pipe 15 and the connecting pipes 13 and 14, and the base stored in the base storage tank 12 is sent to the dripping pipe 15 through the connecting pipes 13 and 14. A pump 16 is provided.

Next, an example of the crystallization operation using the crystallization apparatus 1 will be described below.
First, a raw material organic acid salt solution is prepared by dissolving the raw material organic acid salt in water or alkali. Next, the raw organic acid salt solution is introduced into the reaction vessel 2 as a reaction stock solution. Next, the acid stored in the acid storage tank 7 is supplied to the reaction liquid in the reaction vessel 2 from the dropping pipe 10 through the connecting pipes 8 and 9 using the pump 11. For example, the acid is diluted in water to a desired concentration and stored in the acid storage tank 7 in advance. In this embodiment, for example, a 6N hydrochloric acid aqueous solution is used, but the present invention is not limited to this.

  As described above, the organic acid salt in the reaction stock solution reacts with the acid introduced into the reaction vessel 2, whereby the organic acid is converted into a supersaturated state of (II) and a rapid state of (III). After the time of cancellation of the supersaturated state, it reaches the saturated state of (IV) and precipitates as crystals.

  Next, at any point in (IV) above, the base stored in the base storage tank 12 is supplied to the reaction liquid in the reaction vessel 2 from the dropping pipe 15 through the connecting pipes 13 and 14 using the pump 16. Thus, fine crystals in the reaction vessel 2, that is, a part of the precipitated crystals are dissolved.

  The timing of the supply of the base may be after the target organic acid is once crystallized from the raw organic acid salt or after a part of the target organic acid is crystallized from the raw organic acid salt. However, in order to keep the amount of base and acid used as small as possible, it is preferable to supply the base to the reaction liquid at the time when the latter, particularly when crystals are precipitated.

  Precipitation of crystals can be confirmed visually, or a change in pH can be detected using a pH meter utilizing the fact that the pH fluctuates greatly at the moment when the crystals appear. Of course, without confirming the precipitation of crystals, when the number of anionic functional groups in the raw material organic acid salt is 1, the amount of acid added is divided by the equivalent of the acid, and one or more excess amounts are added. May be used to control all the series of reactions to be performed automatically by precipitating crystals.

  Next, the acid stored in the acid storage tank 7 is supplied again from the dropping pipe 10 to the reaction solution in the reaction vessel 2 through the connecting pipes 8 and 9 using the pump 11. Thereby, the organic acid salt of the crystal part dissolved by the base is again subjected to crystallization, and a crystal having a large average particle diameter can be obtained by crystal growth.

  In the crystallization method according to the present embodiment, the supply amount is greater than the value obtained by dividing the added amount (g) of the supplied acid by the equivalent amount (g) of the acid (hereinafter sometimes referred to as the acid equivalent value). The amount of the base added (g) divided by the equivalent (g) of the base (hereinafter sometimes referred to as the base equivalent value) is small, and the anionic functional group contained in the organic acid salt is reduced. In addition to the amount of acid required to acidify all, the amount of acid neutralized by the base is used for the organic acid salt charged. That is, in the crystallization method according to the present embodiment, the amount obtained by dividing the amount of organic acid salt (g) charged by the equivalent amount (g) of the organic acid salt from the acid equivalent value supplied and the base equivalent supplied. The amount of acid and base used is determined so that the sum of the values is small. The amount of the base used may be set so that the amount of the acid excluding the amount neutralized by the base is reduced to the region of (II) above. The value obtained by dividing the amount of organic acid crystals that remained undissolved by supplying the base by the equivalent amount of the organic acid was Q, the amount of the raw material organic acid salt (g) was P, and the molecular weight of the raw material organic acid salt was the organic acid. When the value obtained by dividing the salt molecule by the number of anionic functional groups is Z, Q / (P × Z) is usually in the range of 0.01 to 0.3, preferably 0.05 to 0.2. What is necessary is just to set the usage-amount of the said base so that it may exist in this range. Thereby, a crystal growth period becomes long and a high effect can be acquired.

  For example, when the organic acid is adipic acid, the amount of crystals that remain undissolved even when a base is supplied is usually 1 to 5 of the total crystals precipitated when the raw material organic acid salt is completely reacted with the acid. What is necessary is just to add the said base so that it may become in the range of 30 weight% (in other words, in the range of 1-30 weight% of the prepared organic acid salt), preferably in the range of 5-20 weight%.

  More specifically, in the above reaction, the value obtained by dividing the acid equivalent value added first by (P × Z) is usually in the range of 0.33 to 3, preferably 0.5 to 1. Within the range of 3. In addition, the value obtained by dividing the base equivalent value to be used by (P × Z) is usually 0.03 to 0.3 subtracted from the value obtained by dividing the acid equivalent value to be added first by (P × Z). It is within the range of the value, and preferably within the range of the value obtained by subtracting 0.05 to 0.15 from the value obtained by dividing the acid equivalent value added first by (P × Z). For the value obtained by dividing the acid equivalent value used after dropping the base by the (P × Z), the value obtained by dividing the acid equivalent value used first by the (P × Z) and the acid equivalent value used after dropping the base are The value obtained by subtracting the value obtained by dividing the base equivalent value used by the sum of the value divided by (P × Z) by (P × Z) is usually within the range of 0.9 to 3, preferably It is in the range of 1 to 1.3.

  The supply time, supply position, and supply method of the acid and base are not particularly limited, and the acid and base supply line 4 or the base supply line 4 having the above-described configuration are not necessarily used for supplying the acid and base. Needless to say, the dropping pipes 10 and 15 are not necessarily required for supplying the acid and the base. Further, when the dropping pipes 10 and 15 are used, the dropping pipes 10 and 15 can be provided at arbitrary positions of the reaction vessel 2.

  In addition, the material, size, and the like of each member constituting the crystallizer 1 are not particularly limited as long as they can be used for the reaction between the raw material organic acid salt and an acid or a base.

  Furthermore, the input amount of the reaction stock solution into the reaction vessel 2 may be appropriately set according to the concentration of the crystallization target component, the amount of acid and base used, and the like, and is not particularly limited.

  In addition, the conditions such as the reaction time, reaction temperature, and reaction pressure in each of the reactions described above may be set as appropriate according to the type and amount of the starting organic acid salt, a combination with an acid or a base, and the like. is not.

  During crystallization, by adding acid and base to the above reaction stock solution, the amount of the reaction solution increases slightly. Therefore, the reaction vessel 2 and reaction conditions considering the increase in the amount of the solution are set. It is desirable to use it.

Next, the second method will be described.
As the second method, when the reverse reaction is performed while performing the normal reaction in the same reaction vessel as described above, the crystallizer 1 shown in FIG. 1 is used as the crystallizer used in the method. Can do.

  As the reaction vessel 2 (crystallization reaction tank) used in the second method, a stirring tank with a stirrer equipped with a disk turbine blade, a paddle blade, a retracted blade such as a three-sheet retracted blade, an anchor blade, and the like, A reaction vessel similar to the reaction vessel 2 used in the first method can be used. The reaction vessel 2 is not particularly limited as long as it can be used for the reaction of an organic acid salt with an acid and a base, and the scale (capacity), shape, material and the like are not particularly limited.

  Also in the second method, the reaction vessel 2 has a jacket on the outer wall side of the reaction vessel that can cool or heat the reaction liquid in the reaction vessel through the reaction vessel, for example, by conduction of a refrigerant or a heat medium. A reaction vessel having the following is preferably used. The reaction vessel 2 having such a jacket facilitates control of the reaction temperature, such as removal of heat of neutralization.

The number of revolutions of stirring by the stirrer 5 (stirring blade) is preferably set so that the stirring power per unit volume in the reaction vessel 2 is in the range of 0.05 to 2.0 kW / m ³ . More preferably, it is set to be in the range of 05 to 0.3 kW / m ³ .

  Further, the reaction vessel 2 may have a baffle such as a plate baffle, a beaver tail baffle, a finger baffle, a disk baffle, a donut baffle, etc. in addition to the stirring blade. In particular, as the second method, as shown in the above (2), when the reverse reaction is performed while performing the normal reaction in the same reaction vessel 2, the inside of the reaction vessel 2 is partially baffled or the like in this way. It is possible to prevent the acid and the base from being wasted due to neutralization.

Even in this case, each of the dropping tubes 10 and 15 can be provided at an arbitrary position of the reaction vessel 2 shown in FIG. In the case of adding, the acid and the base are hardly mixed with each other from the flow pattern in the reaction vessel 2 in the reaction vessel 2 to be used in order to suppress the wasteful consumption of the acid and the base due to neutralization. It is desirable to supply the position, that is, the position where the dropped acid and base are difficult to contact with each other, and it is desirable that both the dripping pipes 10 and 15 be provided as far as possible from each other.

  In the crystallizer 1 shown in FIG. 1, an acid supply dropping tube 10 is provided at the bottom of the reaction vessel 2, while a base supply dropping tube 15 is provided for the reaction solution in the reaction vessel 2. Provided above the liquid level, that is, at the top in the reaction vessel 2, whereby the acid is supplied to the bottom of the reaction vessel 2 and the base is supplied to the top of the reaction vessel 2. However, as long as both the dripping pipes 10 and 15 are formed at positions separated from each other as described above, the present invention is not limited to this.

  However, since fine crystals tend to move upward by stirring, as shown in FIG. 1, the acid is used in the vicinity of the stirrer 5 (stirring blade) in the reaction vessel 2 using the dropping pipes 10 and 15. In addition, the base may be supplied to the surface of the reaction liquid which is a stirring liquid. That is, in the crystallizer 1, the acid supply dropping tube 10 is provided at the bottom of the reaction vessel 2, and the base supply dropping tube 15 is provided at the top of the reaction vessel 2. It is desirable for producing crystals having a large average particle size by reducing fine crystals.

Next, an example of the crystallization operation using the crystallization apparatus 1 in the second method will be described below.
First, a raw material organic acid salt solution is prepared by dissolving the raw material organic acid salt in water or alkali. Next, the raw organic acid salt solution is introduced into the reaction vessel 2 as a reaction stock solution. Up to this point, the method is the same as the first method. However, when the method (2) is used, the acid stored in the acid storage tank 7 using the pump 11 is transferred to the dropping tube 10 through the connecting tubes 8 and 9. The base stored in the base storage tank 12 using the pump 16 is supplied from the dropping pipe 15 to the reaction liquid in the reaction container 2 through the connecting pipes 13 and 14 while being supplied to the reaction liquid in the reaction container 2 from above. Supply.

  In this case, in order to efficiently perform the normal reaction and the reverse reaction, it is desirable to start supplying the base after the crystal starts to precipitate after the start of supplying the acid.

  In the reaction solution, a normal reaction occurs predominantly near the acid supply position, and a reverse reaction occurs predominantly near the base supply position. The crystals precipitated in the vicinity of the acid supply position dissolve fine crystals in the vicinity of the base supply position by stirring, and the remaining crystals grow in the vicinity of the acid dropping position. In the above method, this reaction is repeated in the reaction vessel 2, and the remaining crystals gradually become larger crystals.

  In the crystallization method as described above, the acid and base are adjusted so that the sum of the amount of the raw material organic acid salt divided by the equivalent amount of the organic acid salt and the supplied base equivalent value is smaller than the acid equivalent value to be supplied. The amount of use is determined.

  The value obtained by dividing the base equivalent value to be used by the (P × Z) is usually in the range of 0.5 to 10, and preferably in the range of 0.8 to 2.5.

  The value obtained by dividing the acid equivalent value used by (P × Z) is usually 0.9 to 1.5, preferably 1 to the value obtained by dividing the base equivalent value used by (P × Z). It is in the range which added 0.0-1.3.

  The base may be supplied at a constant speed, but intermittent dropping is more preferable because nonuniformity in the reaction vessel 2 increases and the average particle diameter of the crystal tends to increase.

  In the crystallization method, it is preferable that the base equivalent value relative to the supplied acid equivalent value is relatively large because the average particle diameter of the crystals tends to be large. A higher base concentration is preferred because it tends to increase the average particle size of the crystals.

  In addition, since the usage-amount of a base, dripping time, etc. change with the flow pattern of the said crystallizer 1, ie, the mixing state resulting from the flow pattern of the said reaction container 2 in this case, it optimizes by changing conditions. It is desirable that That is, in the above method, it is desirable to optimize the balance of the stirring conditions, the dropping position, the dropping speed, and the dropping amount so that the reaction vessel 2 has an appropriate stagnation.

  Also, as described above, instead of adding the base directly into the crystallization reaction vessel, the reaction solution is transferred to a reaction vessel different from the crystallization reaction vessel, the base is added, and the above is returned to the crystallization reaction vessel again. A series of reactions may be performed.

  As shown in the above (3), the reaction solution is transferred to a reaction vessel different from the crystallization reaction vessel, a base is added, and the above-described series of reactions are performed again by returning the reaction solution to the crystallization reaction vessel. In addition, referring to FIG. 2, a method in which the normal reaction and the reverse reaction are performed in different reaction vessels and the liquid in the vessel is circulated between the different reaction vessels and the above-described normal reaction and reverse reaction are alternately repeated. Will be described in detail.

FIG. 2 shows an example of a crystallization apparatus suitably used in the above method.
A crystallization apparatus 20 shown in FIG. 2 includes a first reaction vessel 21 as a crystallization reaction vessel for crystallization of a raw organic acid salt with an acid, and crystals precipitated by crystallization in the first reaction vessel 21. A second reaction vessel 31 as a reaction vessel for reverse reaction for dissolving a part of the reaction solution with a base, an acid supply line 40 (acid supply means) for supplying acid into the first reaction vessel 21, and the above A base supply line 50 (base supply line) for supplying a base into the second reaction vessel 31 and a reaction solution circulation line for circulating the reaction solution between the first reaction vessel 21 and the second reaction vessel 31. 60 (reaction liquid circulation means).

  The first reaction vessel 21 is provided with a stirrer 22 for stirring and reacting the reaction stock solution introduced into the first reaction vessel 21. In addition, the first reaction vessel 21 includes a jacket 23 having a conduction port (not shown) serving as an inlet or outlet of a heat medium such as hot water on the outer wall side.

  Similarly, the second reaction vessel 31 is provided with a stirrer 32 for stirring and reacting the reaction solution introduced into the second reaction vessel 31. Further, the second reaction vessel 31 includes a jacket 33 having a conduction port (not shown) serving as an inlet or outlet for a heat medium such as hot water on the outer wall side.

  The acid supply line 40 includes an acid storage tank 41 for storing an acid, hollow connection pipes 42 and 43 serving as an acid supply path (flow path), and an acid for dropping the acid into the first reaction vessel 21. For supplying acid, provided in the dropping pipe 44 and the connecting pipes 42 and 43, the acid stored in the acid storage tank 41 is sent to the dropping pipe 44 through the connecting pipes 42 and 43. The pump 45 is provided.

  The base supply line 50 supplies a base storage tank 51 for storing a base, hollow connection pipes 52 and 53 serving as a base supply path (flow path), and a base to the second reaction vessel 31 by dropping. And a base provided between the dropping pipe 54 and the connecting pipes 52 and 53, and sending the acid stored in the acid storage tank 51 to the dropping pipe 54 through the connecting pipes 52 and 53. A supply pump 55 is provided.

  In addition, each structure of 1st and 2nd reaction container 21 * 31, the acid supply line 40, the base supply line 50, etc., and each reaction stirring rotation speed in each of the 1st and 2nd reaction containers 21 * 31 The crystallization conditions such as are as described above, and can be set similarly to the case of using the crystallization apparatus 1. That is, the crystallization conditions in the crystallizer 20 are that the normal reaction and the reverse reaction are performed using separate reaction vessels, and the first reaction vessel 21 and the second reaction are performed using the reaction solution circulation line 60. The crystallization conditions can be set in the same manner as in the second method using the crystallization apparatus 1 except that the reaction solution is circulated with the reaction vessel 31.

  The reaction liquid circulation line 60 connects the first reaction vessel 21 and the second reaction vessel 31, and sends a reaction solution in the first reaction vessel 21 to the second reaction vessel 31. And a return path for connecting the first reaction vessel 21 and the second reaction vessel 31 and sending the reaction solution in the second reaction vessel 31 to the first reaction vessel 21. .

  The feed path of the reaction liquid circulation line 60 includes a suction pipe 61 for sucking the reaction liquid in the first reaction vessel 21, hollow connection pipes 62 and 63 serving as a reaction liquid flow path, and the connection A reaction solution circulation pump 64 is provided to be interposed between the tubes 62 and 63 and sends the reaction solution in the first reaction vessel 21 to the second reaction vessel 31 through the connection tubes 62 and 63. Is provided.

  The return path of the reaction liquid circulation line 60 includes a suction pipe 67 for sucking the reaction liquid in the second reaction vessel 31, hollow connection pipes 68 and 69 serving as a reaction liquid flow path, A reaction solution circulation pump that is provided between the connection pipes 68 and 69 and sends the reaction solution in the second reaction vessel 31 to the first reaction vessel 21 through the connection tubes 68 and 69. 70 is provided.

  As a result, the reaction liquid in each of the crystallizing apparatuses 21 and 31 is extracted to the pumps 64 and 70 through the connection pipes 62 and 68 by the suction pipes 61 and 67, and further, the connection pipes 63 and 69 are connected. By being introduced into each reaction vessel 21 and 31 through, it circulates between each reaction vessel 21 and 31.

  In addition, as said reaction vessel 21 * 31, although a stirring mixing tank, a line mixer, a static mixer etc. are mentioned, for example, it is not specifically limited. As these reaction vessels 21 and 31, the same reaction vessel as the reaction vessel 2 can be used, and any reaction vessel can be used as long as it can be used for the reaction of the raw organic acid salt with the acid and the base. However, the scale (capacity), shape, material, and the like are not particularly limited.

Next, an example of the crystallization operation using the crystallization apparatus 20 will be described below.
First, a raw material organic acid salt solution is prepared by dissolving the raw material organic acid salt in water or alkali. Next, the raw organic acid salt solution is introduced into the first reaction vessel 21 as a reaction stock solution. Next, the acid stored in the acid storage tank 41 is supplied from the dropping pipe 44 to the reaction solution in the reaction vessel 21 through the connecting pipes 42 and 43 using the pump 45. As described above, the acid is, for example, previously diluted in water to a desired concentration and stored in the acid storage tank 41.

  The raw material organic acid salt in the first reaction vessel 21 reacts with the acid introduced into the first reaction vessel 21 and precipitates as crystals. The reaction liquid in which the precipitated crystals are dispersed is extracted from the first reaction vessel 21 using the suction pipe 61 by the pump 64 provided in the feeding path of the reaction liquid circulation line 60, and connected to the connection pipe 62. It is introduced into the second reaction vessel 31 through 63.

  In the second reaction vessel 31, the base stored in the base storage tank 51 is dropped and supplied from the dropping pipe 54 through the connecting pipes 52 and 53 by the pump 55. For this reason, the crystals in the reaction solution introduced into the second reaction vessel 31 react with the base supplied into the second reaction vessel 31 to partially dissolve, and the reaction solution contains Only relatively large crystals remain. Note that, as described above, the base is diluted in water to a desired concentration and stored in the base storage tank 51 in advance, for example.

  The reaction solution in which fine crystals are dissolved in the second reaction vessel 31 is removed from the second reaction vessel 31 using the suction pipe 67 by the pump 70 provided in the return path of the reaction solution circulation line 60. It is extracted and returned to the first reaction vessel 21 through the connecting pipes 68 and 69.

  In the first reaction vessel 21, new crystals are generated by the acid dropped and supplied from the acid storage tank 41 through the dropping tube 44, while the reaction solution circulated through the second reaction vessel 31 is generated. The crystal is grown as a nucleus (seed crystal).

  The reaction liquid in the first reaction vessel 21 is again introduced into the second reaction vessel 31 through the delivery path of the reaction solution circulation line 60, and here, the finely newly produced in the first reaction vessel 21. New crystals are dissolved and returned to the first reaction vessel 21 again. By repeating this, a crystal having a larger average particle diameter is produced.

  When the crystallizer 20 is used, a base is supplied to the second reaction vessel 31, and the reaction solution supplied to the second reaction vessel 31 through the reaction liquid circulation line 60. In the return path of the reaction liquid circulation line 60, a relatively large crystal is returned to the first reaction vessel 21 through the return path of the reaction liquid circulation line 60 by dissolving the fine crystals therein. Can be observed.

  If the crystallizer 20 described above is used, the circulation of the reaction solution can be controlled by the pumps 64 and 70, the circulation amount, the timing of delivery of the reaction solution, and the like. Therefore, by using the crystallizer 20 described above, for example, the reaction time in each of the above reaction vessels, that is, the first reaction vessel 21 and the second reaction vessel 31 can be adjusted. Needless to say, the crystallization can be performed using the crystallization apparatus 20 in a state where the reaction liquid is always circulated.

  The crystallization conditions when using the crystallization apparatus 20 described above are set similarly to the crystallization conditions in the second method using the crystallization apparatus 1.

For example, the rotation speed of stirring by the stirrer 22 (stirring blade) is set so that the stirring power per unit volume in the first reaction vessel 21 is in the range of 0.05 to 2.0 kW / m ^3. It is preferable that it is set to be in the range of 0.05 to 0.3 kW / m ³ .

However, when the crystallizer 20 described above is used, on the base supply side, the stirring rotation speed is sufficient if it is sufficient to dissolve the crystals. For example, the stirring rotation by each of the above stirrers 32 (stirring blades). The number is preferably set so that the stirring power per unit volume in the second reaction vessel 31 is in the range of 0.1 to 2.0 kW / m ³ .

  That is, in the stirrer 22, it is desirable to stir relatively slowly so as not to break the crystal. However, the stirrer 32 is not particularly limited, and it is preferable to stir relatively strongly because the crystal can be dissolved quickly. .

  Also in the above crystallization method, the acid is adjusted so that the sum of the amount of the raw material organic acid salt divided by the equivalent amount of the organic acid salt and the supplied base equivalent value is smaller than the acid equivalent value to be supplied. And the amount of base used is determined.

  The value obtained by dividing the base equivalent value to be used by (P × Z) is usually in the range of 0.1 to 2.5, and preferably in the range of 0.75 to 1.5.

  Further, the value obtained by dividing the acid equivalent value used by (P × Z) is usually 0.9 to 1.5, preferably the value obtained by dividing the equivalent value of the base used by (P × Z). Is within the range of the value obtained by adding 1.0 to 1.2.

  However, in the above method, the amount of the base used is preferably that the reaction vessel 31 is alkaline for a long time, the amount of raw material organic acid salt (g) is P, and the molecular weight of the raw material organic acid salt is organic The value obtained by dividing the number of anionic functional groups possessed by one molecule of the acid salt is Z, the base equivalent value (the value obtained by dividing the base addition amount (g) by the equivalent (g) of the base) is M, and the dropping time is T (min ), The circulation rate of the reaction liquid per unit time is F (ml / min), the logarithmic average of the maximum liquid volume and the minimum liquid volume in the system, that is, the crystallizer 20 (that is, the first reaction vessel 21 and Assuming that L (ml) is the logarithmic average of the maximum amount and the minimum amount of the total amount of the liquid in the second reaction vessel 31 and the liquid in the connecting pipes 62, 63, 68, and 69, (L × M) / Within a range where the value (α) represented by (T × F × P × Z) is 0.5 or more and less than 1.5, preferably Or it is desirable to set it within the range of 0.7 or more and less than 1.1.

  In the crystallization apparatus 20 shown in FIG. 2, the reaction liquid is extracted from the first reaction vessel 21 and the second reaction vessel 31 using the suction tubes 61 and 67, but the present invention is not limited to this. For example, a reaction liquid discharge port may be provided in the bottom or peripheral wall of the first reaction container 21 and the second reaction container 31, and the reaction liquid may be extracted from the reaction liquid discharge port. That is, the connecting pipes 62, 63, 68, and 69 and the suction pipes 61 and 67 that constitute the reaction liquid circulation line 60 are also connected to arbitrary portions of the reaction vessels 21 and 31, like the dropping pipes 44 and 54. can do.

  In the crystallizer 20 shown in FIG. 2, the reaction solution discharged from the first reaction vessel 21 is supplied to the upper portion of the second reaction vessel 31 through the reaction solution circulation line 60, and the reaction solution circulation is performed. Although the reaction solution discharged from the second reaction vessel 31 is supplied to the upper part of the first reaction vessel 21 by the return path of the line 60, the configuration of the crystallizer 20 is limited to this. It is not something. A plurality of reaction vessels, supply lines, circulation lines, and the like may be provided.

  Also in the second method, the conditions such as the amount of the reaction liquid initially charged into the first reaction vessel 31, the reaction time and reaction temperature in each reaction, the reaction pressure, etc. It may be set as appropriate according to the amount, combination with acid or base, and is not particularly limited.

  The organic acid crystal solution thus obtained can be isolated by ordinary filtration. As a filtration method, for example, any filtration method such as centrifugal filtration, pressure filtration, vacuum filtration, natural flow filtration, or the like may be employed.

  As described above, according to the present embodiment, fine crystals can be reduced by crystallization by the above-described crystallization methods, and the ratio of organic acids used for crystal growth can be increased. Since crystals can be grown well, crystals having a large average particle diameter and powders having a large bulk density can be stably obtained with good reproducibility.

  It is expected that the average particle size of the crystals obtained using the above crystallization methods is shifted to the large particle side. As a result, when the reaction solution containing the crystal is separated by filtration, the effect of improving the filterability of the reaction solution, and the obtained organic acid powder has a high bulk density and fluidity. The effect of improving can be acquired.

  The present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims. That is, embodiments obtained by combining technical means appropriately modified within the scope of the claims are also included in the technical scope of the present invention.

  EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention further in detail, this invention is not limited at all by these.

[Example 1]
In a 1000 ml separable flask (reaction vessel) equipped with three receding blades (stirrer) with a radius of 30 mm, 12.02 g of salicylic acid, 15.17 g of 8 mol / l (20 ° C.) sodium hydroxide aqueous solution and 499.87 g of water were added. In addition, salicylic acid was completely dissolved to obtain a raw material organic acid salt solution (reaction stock solution).

  Subsequently, the stirring speed of the three blades was set at 370 rpm, and 19.14 g of 6 mol / l (20 ° C.) hydrochloric acid was applied to the surface of the separable flask using a metering pump at an internal temperature of 30 ° C. Was added dropwise over 29 minutes. At 7 minutes from the start of the dropwise addition of hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, 11.02 g of an 8 mol / l sodium hydroxide aqueous solution (20 ° C.) was charged over 8 minutes on the surface of the liquid in the separable flask, and then the surface of the liquid in the separable flask using a metering pump. 12.75 g of 6 mol / l (20 ° C.) hydrochloric acid was added dropwise over 20 minutes.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain 10.35 g of salicylic acid crystals. Next, the volume-based average diameter of the crystal was measured with a laser diffraction particle size distribution analyzer (“Master Sizer S Long bed” (trade name) manufactured by Malvarn Instruments Ltd., UK). It was 8 μm.

[Comparative Example 1]
In a 1000 ml separable flask (reaction vessel) equipped with three retreating blades (stirrer) with a radius of 30 mm, 12.02 g of salicylic acid, 15.18 g of an 8 mol / l (20 ° C.) sodium hydroxide aqueous solution and 500.01 g of water were added. In addition, salicylic acid was completely dissolved to obtain a raw material organic acid salt solution (reaction stock solution).

  Subsequently, the stirring rotation speed of the three retreat blades was set to 370 rpm, and 19.15 g of 6 mol / l (20 ° C.) hydrochloric acid was applied to the surface of the separable flask using a metering pump at an internal temperature of 30 ° C. Was added dropwise over 30 minutes. At 10 minutes after the start of the dropwise addition of hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, the reaction liquid in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain 9.97 g of salicylic acid crystals. Subsequently, when the volume reference average diameter of the crystal was measured with the same laser diffraction particle size distribution analyzer as in Example 1, the volume reference average diameter was 53.3 μm.

[Example 2]
In a 500 ml separable flask (reaction vessel) equipped with three receding blades (stirrer) with a radius of 23 mm, 14.62 g of adipic acid, 17.53 g of an 8 mol / l (20 ° C.) sodium hydroxide aqueous solution, 199.01 g of water Then, adipic acid was completely dissolved to prepare a raw organic acid salt solution (reaction stock solution).

  Subsequently, the stirring rotation speed of the three retreat blades was set to 171 rpm, and 40.26 g of 6 mol / l (20 ° C.) hydrochloric acid was added to the Separa using a dropping funnel (dropping tube) at an internal temperature of 30 ° C. The solution was added dropwise to the bottom of the bull flask over 40 minutes.

  Sixteen minutes after the start of dropping hydrochloric acid, 15.95 g of an 8 mol / l (20 ° C.) aqueous sodium hydroxide solution was added to the surface of the reaction solution in the separable flask using a dropping funnel. At the same time, dropwise addition was performed, and the dropwise addition was completed in 24 minutes.

  Thereafter, the dropping funnel for dropping hydrochloric acid and the dropping funnel for dropping sodium hydroxide used in the above reaction were washed with 3.19 g and 2.08 g of water, respectively.

Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain adipic acid crystals. Subsequently, when the volume standard average diameter of the crystal was measured by the same laser diffraction type particle size distribution measuring machine as in Example 1, the volume standard average diameter was 175 μm. When 1.50 g of the obtained adipic acid crystal was charged into a glass tube having an inner diameter of 8 mm, the height of the powder was 90 mm and the bulk density of the powder was 332 kg / m ³ .

[Comparative Example 2]
To a 500 ml separable flask equipped with three receding blades with a radius of 23 mm, 14.62 g of adipic acid, 17.53 g of 8 mol / l (20 ° C.) sodium hydroxide aqueous solution and 199.04 g of water were added, and adipic acid was completely removed. To obtain a raw material organic acid salt solution (reaction stock solution).

  Subsequently, 21.96 g of 6 mol / l (20 ° C.) hydrochloric acid was added to the separable flask using a dropping funnel at an internal temperature of 30 ° C. with a stirring rotation speed of the three blades set to 316 rpm. The solution was dropped onto the surface of the reaction solution over 26 minutes, and the dropping funnel was washed with 4.12 g of water.

  Subsequently, the reaction liquid in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain adipic acid. Subsequently, when the volume standard average diameter of the crystal was measured by the same laser diffraction type particle size distribution measuring machine as in Example 1, the volume standard average diameter was 129 μm.

When 1.50 g of the obtained adipic acid crystals were charged into a glass tube having an inner diameter of 8 mm, the height of the powder was 112 mm and the bulk density of the powder was 267 kg / m ³ .

Example 3
In a 1000 ml separable flask (first reaction vessel) equipped with three receding blades (stirrer) having a radius of 30 mm, biotin 50.13 g, 8 mol / l (20 ° C.) sodium hydroxide aqueous solution 35.88 g, water 600 0.1 g was added to completely dissolve biotin to obtain a raw material organic acid salt solution (reaction stock solution), and the stirring speed of the three-bladed blade was set to 300 rpm. Further, 100.22 g of water was added to a 500 ml separable flask (second reaction vessel) equipped with a three-bladed blade (stirrer) having a radius of 23 mm, and the stirring rotation speed of the three-blade blade was set to 350 rpm. . A dip tube is installed in the first reaction vessel, and the content (reaction solution) in the first reaction vessel is transferred to the content in the second reaction vessel at 32.8 ml / min by a pump. The solution was sent to the liquid surface. At the same time, a dip tube is installed in the second reaction vessel, and the content (reaction solution) in the second reaction vessel is pumped at 32.8 ml / min with the content in the first reaction vessel. The solution was sent to the surface of the product, and the contents in both reaction vessels were circulated for 10 minutes.

  Subsequently, while continuing circulation at the above flow rate, 101.25 g of 6 mol / l (20 ° C.) hydrochloric acid was added to the liquid surface in the first reaction vessel for 45 minutes using a metering pump at an internal temperature of 30 ° C. It was dripped over. At the same time, while continuing circulation at the above flow rate, 48.96 g of an 8 mol / l (20 ° C.) sodium hydroxide aqueous solution was added to the liquid in the contents of the second reaction vessel using a metering pump at an internal temperature of 30 ° C. It was dripped on the surface over 45 minutes.

After completion of dropping, the contents in both reaction vessels were circulated at the above flow rate for 10 minutes. Subsequently, the reaction liquid in both reaction vessels was filtered under reduced pressure and then dried under reduced pressure to obtain 49.83 g of biotin crystals. Subsequently, when the volume standard average diameter of the crystal was measured with the same laser diffraction type particle size distribution analyzer as in Example 1, the volume standard average diameter was 24.1 μm. In addition, the UtoTakashi density and Mitsukasa density of the crystal was measured in the powder properties measuring device (Hosokawa Micron of "Powder Tester" (trade name)), met each ^{219kg / m 3, 402kg / m} 3 It was.

[Comparative Example 3]
In a 1000 ml separable flask (reaction vessel) equipped with three retreating blades (stirrer) with a radius of 30 mm, biotin (50.02 g), 8 mol / l (20 ° C.) sodium hydroxide aqueous solution (35.87 g) and water (700.1 g) were added. In addition, biotin was completely dissolved to obtain a raw material organic acid salt solution (reaction stock solution), and the number of stirring rotations of the three-bladed blade was set to 300 rpm. Subsequently, 44 mol. L (6 mol / l (20 ° C.)) hydrochloric acid (44.93 g) was dropped onto the surface of the content (reaction liquid) in the separable flask over 40 minutes using a metering pump at an internal temperature of 30 ° C. .

Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain 49.96 g of biotin crystals. Subsequently, when the volume standard average diameter of the crystal was measured with the same laser diffraction type particle size distribution measuring machine as in Example 3, the volume standard average diameter was 14.6 μm. Further, the UtoTakashi density and Mitsukasa density of the crystal was measured in the same powder properties measuring instrument as in Example 3 were respectively ^{188kg / m 3, 348kg / m} 3.

Example 4
In a 500 ml separable flask (reaction vessel) equipped with three receding blades (stirrer) with a radius of 23 mm, 20.13 g of nicotinic acid, 28.50 g of an 8 mol / l (20 ° C.) sodium hydroxide aqueous solution, 300.73 g of water Was added to completely dissolve nicotinic acid to obtain a raw organic acid salt solution (reaction stock solution). Subsequently, the stirring rotation speed of the three retreat blades was set to 300 rpm, and 6 mol / l (6 mol / l) was applied to the liquid surface of the content (reaction liquid) in the separable flask using a dropping funnel at an internal temperature of 5 ° C. (20 ° C.) 36.38 g of hydrochloric acid was added dropwise over 3 minutes. At 1 minute and 10 seconds from the start of the dropwise addition of hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, 20.71 g of an 8 mol / l (20 ° C.) sodium hydroxide aqueous solution was charged on the surface of the contents in the separable flask, and then the contents in the separable flask were added using a dropping funnel. To the liquid surface, 24.02 g of 6 mol / l (20 ° C.) hydrochloric acid was dropped over 2 minutes.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain 13.28 g of nicotinic acid crystals. Subsequently, when the volume standard average diameter of the crystal was measured with the same laser diffraction type particle size distribution measuring machine as in Example 1, the volume standard average diameter was 20.4 μm.

[Comparative Example 4]
In a 500 ml separable flask (reaction vessel) equipped with three receding blades (stirrer) with a radius of 23 mm, 20.02 g of nicotinic acid, 28.49 g of an 8 mol / l (20 ° C.) sodium hydroxide aqueous solution and 300.31 g of water Was added to completely dissolve nicotinic acid to obtain a raw organic acid salt solution (reaction stock solution).

  Subsequently, the stirring rotation speed of the three blades was set to 300 rpm, and the content (reaction liquid) in the separable flask was added to the surface of the separable flask at a temperature of 5 ° C. using a dropping funnel. 20 ° C.) hydrochloric acid (36.16 g) was added dropwise over 3 minutes. At 1 minute and 10 seconds from the start of the dropwise addition of hydrochloric acid, a rapid crystal precipitation was visually observed.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and then dried under reduced pressure to obtain 14.10 g of nicotinic acid crystals. Subsequently, when the volume standard average diameter of the crystal was measured by the same laser diffraction type particle size distribution measuring instrument as in Example 1, the volume standard average diameter was 18.4 μm.

  The present invention relates to a method for crystallizing an organic acid comprising adding an acid to an organic acid salt solution to produce a crystal having a large average particle size and bulk density, and a crystallizer suitable for the method. As described above, the filtration operation is facilitated and has various usefulness. Therefore, the present invention can be used not only in the production of organic acids but also in various chemical industries such as pharmaceutical manufacturing industry using organic acids as raw materials, agricultural chemical manufacturing industry, food manufacturing industry, industrial chemical manufacturing industry such as additives, etc. It is.

It is a schematic diagram which shows the structure of the crystallization apparatus used for the crystallization method of this invention. It is a schematic diagram which shows the structure of the other crystallization apparatus used for the crystallization method of this invention.

Explanation of symbols

1 Crystallizer 2 Reaction vessel (crystallization reaction tank)
3 Acid supply line (acid supply means)
4 Base supply line (base supply means)
5 Stirrer 7 Acid storage tank 8 Connection pipe 9 Connection pipe 10 Dropping pipe 12 Base storage tank 13 Connection pipe 14 Connection pipe 15 Dropping pipe 20 Crystallizer 21 First reaction vessel 22 Stirrer 31 Second reaction vessel 32 Stirrer 40 Acid Supply line (acid supply means)
41 Acid storage tank 42 Connecting pipe 43 Connecting pipe 44 Dropping pipe 50 Base supply line (base supply means)
51 Base storage tank 51 Acid storage tank 52 Connection pipe 53 Connection pipe 54 Dropping pipe 60 Reaction liquid circulation line (reaction liquid circulation means)
61 suction pipe 62 connection pipe 63 connection pipe 67 suction pipe 68 connection pipe 69 connection pipe

Claims (8)

A method for crystallizing an organic acid that is hardly soluble or insoluble in water, comprising crystallization of an organic acid by adding an acid to an organic acid salt solution,
By adding an acid to the solution of the organic acid salt, after precipitating at least a portion of the organic acid crystals of the total organic acid crystals precipitated, by adding a base to the solution containing the organic acid crystals, the organic acid A method for crystallizing an organic acid, comprising converting a part of the crystal into an organic acid salt and dissolving the solution, and adding an acid to the solution of the organic acid salt. A method for crystallizing an organic acid that is hardly soluble or insoluble in water, comprising crystallization of an organic acid by adding an acid to an organic acid salt solution,
After the organic acid crystals began to precipitate by adding an acid to the solution of the organic acid salt, and adding a base to the solution containing the organic acid crystals to convert a portion of the organic acid crystals in an organic acid salt while dissolving Te, crystallization method of the organic acids include performing the addition of acid. Acid addition and base addition are performed in separate reaction vessels provided in communication with each other while circulating the solution in the reaction vessel between the reaction vessels, and the organic acid salt solution before the initial acid addition equivalents of an organic acid salt amount (g) P, a value obtained by dividing the molecular weight of the organic acid salt with an anionic functional groups possessed by the organic acid salt 1 molecule Z, amount of base (g) said base in The value divided by (g) is M, the addition time is T (min), the circulation amount of the liquid per unit time is F (ml / min), and the logarithmic average of the maximum and minimum liquid amounts in the system is L. (Ml) The amount of the base is adjusted so that the value of the formula represented by L × M / (T × F × P × Z) satisfies 0.5 or more and less than 1.5. 2. The method for crystallizing an organic acid according to 2 . Below M / (P × Z) is crystallization method of an organic acid according to any one of ranges der Ru claims 1-3 which satisfy the following equation.
Q / (P × Z) −0.3 ≦ M / (P × Z) ≦ Q / (P × Z) −0.03
M: Value obtained by dividing the amount of base added (g) by the equivalent amount of the base (g)
Q: Value obtained by dividing the amount (g) of the acid added before the base addition by the equivalent amount (g) of the acid
P: amount of organic acid salt in solution of organic acid salt before addition of initial acid (g)
Z: Value obtained by dividing the molecular weight of the organic acid salt in the organic acid salt solution before the initial acid addition by the number of anionic functional groups of one molecule of the organic acid salt The method for crystallization of an organic acid according to any one of claims 1 to 4, wherein the amount of the organic acid crystals remaining after the addition of the base is in the range of 1 to 30% by weight of the total crystals to be precipitated . An organic acid crystal is isolated from a step of obtaining an organic acid crystal using the organic acid crystallization method according to any one of claims 1 to 5 and a reaction solution containing the organic acid crystal obtained by the step. The manufacturing method of the organic acid crystal including a process . A crystallization reaction container, an acid supply means for supplying an acid into the crystallization reaction container, and a base supply means for supplying a base into the crystallization reaction container, the acid supply means and the base supply means, An apparatus for crystallizing an organic acid hardly soluble or insoluble in water, comprising supplying an acid and a base to positions separated from each other in the crystallization reaction vessel . A first reaction vessel provided with an acid supply means; a second reaction vessel provided with a base supply means; and the first reaction vessel and the second reaction vessel communicated with each other; An apparatus for crystallizing an organic acid that is hardly soluble or insoluble in water, comprising a liquid circulating means for circulating the reaction liquid between the second reaction vessel and the second reaction container .

Images